A Mediterranean Diet for Colon Cancer Prevention: Epidemiological and animal studies indicate that the major components of the traditional Cretan-Mediterranean diet have great promise for the prevention of colorectal cancer while improving overall health. Relative to the American diet, the Mediterranean diet is lower in n-6 fatty acids, polyunsaturated fats, and red meat while intakes of plant-based foods and monounsaturated fats are higher. The hypothesis behind this proposal is that adherence to a Mediterranean type of diet will result in a decrease in n-6 fatty acids and increased n-3 and n-9 fatty acids in human colonic mucosa. This, together with other aspects of the diet such as increased intakes of phytochemicals in fruits and vegetables, is expected to modulate eicosanoid metabolism in normal colorectal mucosa to its anticarcinogenic state resulting in lower colonic proliferation. We will recruit 120 study participants who are at increased risk of colorectal cancer. Subjects will be randomized to a modified Mediterranean diet or a Healthy People 2010 diet for 6 months. The Mediterranean diet will be designed to decrease polyunsaturated fat intake and to increase intakes of monounsaturated fats, fruits and vegetables. These dietary changes are expected to not only decrease pro-inflammatory mediators and increase anti-inflammatory mediators, but to also change the types of eicosanoids that are produced from cyclooxygenases and lipoxygenases. Our pilot testing of this novel exchange list diet indicates that subjects can make very large dietary changes. Dietary intake data, blood samples and biopsies of normal mucosa from flexible sigmoidoscopy will be analyzed before and after intervention, and changes from baseline will be compared in the 2 diet arms. The specific endpoints are fatty acids and carotenoids in blood and mucosa, the types and levels of inflammatory mediators in the mucosa, and proliferation in the mucosa. We expect that the Healthy People 2010 diet will result in minimal changes relative to the Mediterranean diet. Increasing our understanding of the effects of dietary changes on human mucosa is fundamental to evaluating the potential of diet in colorectal cancer prevention. Such data would also validate the use of these biomarkers as screen for other dietary and/or pharmaceutical-based interventions aimed at slowing or reversing carcinogenesis. If beneficial effects can be demonstrated in mucosal biomarkers of colorectal cancer risk (prostaglandin E2, other eicosanoids, proliferation), such data may be used to justify a larger, prospective intervention with disease endpoints and more detailed dietary studies.